Chromosome 1 C-band length mosaicism was detected in lymphocytes from six tumor patients and one healthy subject belonging to three families with a high incidence of cancer. In all cases the variant cell population showed a decreased amount of C-heterochromatin in one chromosome, whereas the C-banded pattern of the homolog was identical to that of the nonvariant cell population. A family tendency to unequal mitotic crossing over, possibly leading to C-band heteromorphism, may explain the high frequency of detection of C-heterochromatin mosaicism in cancer family members (seven of 13 cases studied). The possible role of heterochromatin in inducing cancer has been widely discussed. The special feature of the acquired C-band variants vis-à-vis the inherited ones is that they mark intrinsic genetic instability that may result, through multiple mechanisms, in increased susceptibility to malignancy.